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Although generally thought of as distinct diseases, the intersectional overlap between CVD and cancer is increasingly evident in both causal and mechanistic relationships. The field of cardio-oncology is largely focused on the cardiotoxic effects of cancer therapies (e.g., chemotherapy, radiation). Furthermore, the cumulative effects of cardiotoxic therapy exposure and the prevalence of CVD risk factors in patients with cancer lead to long-term morbidity and poor quality of life in this patient population, even when patients are cancer-free. Evidence from patients with cancer and animal models demonstrates that the presence of malignancy itself, independent of cardiotoxic therapy exposure or CVD risk factors, negatively impacts cardiac structure and function. As such, the primary focus of this review is the cardiac pathophysiological and molecular features of therapy-na\u00efve cancer. We also summarize the strengths and limitations of preclinical cancer models for cardio-oncology research and discuss therapeutic strategies that have been tested experimentally for the treatment of cancer-induced cardiac atrophy and dysfunction. Finally, we explore an adjacent area of interest, called \u201creverse cardio-oncology,\u201d where the sequelae of heart failure augment cancer progression. 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